Oxidative Stress in the Pathogenesis of Crohn’s Disease and the Interconnection with Immunological Response, Microbiota, External Environmental Factors, and Epigenetics

Abstract

Inflammatory bowel disease (IBD) is a complex multifactorial disorder in which external and environmental factors have a large influence on its onset and development, especially in genetically susceptible individuals. Crohn’s disease (CD), one of the two types of IBD, is characterized by transmural inflammation, which is most frequently located in the region of the terminal ileum. Oxidative stress, caused by an overabundance of reactive oxygen species, is present locally and systemically in patients with CD and appears to be associated with the well-described imbalanced immune response and dysbiosis in the disease. Oxidative stress could also underlie some of the environmental risk factors proposed for CD. Although the exact etiopathology of CD remains unknown, the key role of oxidative stress in the pathogenesis of CD is extensively recognized. Epigenetics can provide a link between environmental factors and genetics, and numerous epigenetic changes associated with certain environmental risk factors, microbiota, and inflammation are reported in CD. Further attention needs to be focused on whether these epigenetic changes also have a primary role in the pathogenesis of CD, along with oxidative stress.

Oxidative Stress Does Not Influence Subjective Pain Sensation in Inflammatory Bowel Disease Patients

“…To preserve cellular homeostasis, the activity of prooxidants has to be compensated for by antioxidants. Antioxidant enzymes SOD, CAT, and GPX, are present in cells and have a primary role in detoxification [ 2 ]. Mrowicka et al found significantly lower SOD, CAT and GPX levels in IBD patients in relation to controls [ 1 ].…”

“…Inflammatory bowel diseases (IBDs), including Crohn’s disease (CD) and ulcerative colitis (UC), are chronic ailments of multifactorial etiology, affecting mostly the gastrointestinal (GI) tract [ 1 ]. IBD is a result of a complex interplay between genetic factors, changes in the colonic barrier function, immune system, intestinal microbiota, and environmental factors, such as diet, smoking, drugs, alcohol, or xenobiotics [ 1 , 2 ]. Constant exposure of the GI tract to risk factors leads to oxidative stress (OS): an overproduction of reactive oxygen species (ROS) and free radicals with accompanying insufficiency of endogenous antioxidant systems [ 3 ].…”

“…OS leads to the damage of the GI’s mucosal layer, which in turn stimulates immune response [ 4 ]. The imbalance between antioxidant systems and overproduction of ROS, generated mostly by phagocytic immune cells that infiltrate the mucosal tissue [ 2 , 3 , 4 ], disrupts cellular homeostasis, as it leads to cell malfunction and injury due to lipid, protein, carbohydrate and nucleic acid damage, thus accelerating and aggravating the inflammation [ 2 , 5 ]. OS, together with the following perpetuation of inflammatory reaction caused by overabundance of ROS, have been proposed as mechanisms involved in the onset, progression, and symptomatology of IBD.…”

“…OS, together with the following perpetuation of inflammatory reaction caused by overabundance of ROS, have been proposed as mechanisms involved in the onset, progression, and symptomatology of IBD. Antioxidant production is the first-line defense against ROS, however in a state of continuous OS those resources are diminished and IBD patients show reduced activity of main antioxidant systems and decreased detoxification [ 2 , 5 ].…”

“…Glutathione (GSH) is a nonenzymatic molecule which protects cells against the overproduction of free radicals. Glutathione peroxidase (GPX), produced mainly by intestinal epithelium, regulates the amount of GSH by catalyzing it into oxidized glutathione (GSSG) [ 2 , 3 ].…”